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  • 8th European Conf Infect Leukaemia; Lehrnbecher, Thomas; Averbuch, Dina; Castagnola, Elio; Kanerva, Jukka; Groll, Andreas H. (2021)
    Paediatric patients with cancer and those undergoing haematopoietic cell transplantation are at high risk of bacterial infections. The 8th European Conference on Infections in Leukaemia (ECIL-8) convened a Paediatric Group to review the literature and to formulate recommendations for the use of antibiotics according to the European Society of Clinical Microbiology and Infectious Diseases grading system. The evaluation of antibacterial prophylaxis included mortality, bloodstream infection, febrile neutropenia, emergence of resistance, and adverse effects as endpoints. Initial antibacterial therapy and antibiotic de-escalation or discontinuation focused on patients with a clinically stable condition and without previous infection or colonisation by resistant bacteria, and on patients with a clinically unstable condition or with previous infection or colonisation by resistant bacteria. The final considerations and recommendations of the ECIL-8 Paediatric Group on antibacterial prophylaxis, initial therapy, and de-escalation strategies are summarised in this Policy Review.
  • Lääveri, Tinja; Vilkman, Katri; Pakkanen, Sari; Kirveskari, Juha; Kantele, Anu (2018)
    Background: Among visitors to the (sub)tropics, 20-50% contract travellers' diarrhoea (TD) and 5-30% take antibiotics. While shortening the duration of illness, antimicrobials predispose to acquisition of multi-drug resistant bacteria. Therefore, liberal use is no longer advocated. Although antibiotics kill pathogens, no data support the view that they could prevent post-infectious sequelae. We investigated how antibiotic use for TD abroad impacts the pathogen findings at return. Materials and methods: We revisited 456 travellers' clinical data and stool pathogens examined by qPCR for Salmonella, Yersinia, Campylobacter, Shigella, Vibrio cholerae and enteroaggregative (EAEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC) and enteroinvasive (EIEC) Escherichia coli. Results: Among travellers with TD, antibiotic users had pathogen-positive samples less frequently than non-users (50% versus 83%). The difference was significant for EPEC (23% versus 47%) and EAEC (27% versus 54%), but not ETEC (17% versus 26%) or the other pathogens. Shigella/EIEC was found more often among antibiotic users than non-users (4% versus 1%). Conclusion: Despite antibiotic treatment of TD, half of the users still had stool pathogens at return, reflecting either antibiotic resistance of pathogens or recolonisation/reinfection while abroad. Treatment of TD with antibiotics during travel should not be interpreted to indicate eradication of pathogens.
  • Kantele, Anu; Mero, Sointu; Kirveskari, Juha; Laaveri, Tinja (2017)
    Background: One third of travellers to the poor regions of the (sub) tropics become colonized by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Co-resistance to non-betalactam antibiotics complicates the treatment of potential ESBL-PE infections. Methods: We analysed co-resistance to non-beta-lactams among travel-acquired ESBL-PE isolates of 90 visitors to the (sub) tropics with respect to major risk factors of colonization: destination, age, travellers' diarrhoea (TD) and antibiotic (AB) use. Results: Of the ESBL-PE isolates, 53%, 52%, 73%, and 2% proved co-resistant to ciprofloxacin, tobramycin, co-trimoxazole, and nitrofurantoin, respectively. The rates were similar among those with (TD+) or without (TD-) travellers' diarrhoea. Among fluoroquinolone-users vs. AB non-users, the co-resistance rates for ciprofloxacin were 95% versus 37% (p = 0.001), for tobramycin 85% versus 43% (p = 0.005), co-trimoxazole 85% versus 68% (p = 0.146), and nitrofurantoin 5% versus 2% (p = 0.147). In multivariable analysis co-resistance to ciprofloxacin was associated with increasing age, fluoroquinolone use, and tobramycin resistance. Conlusions: While TD predisposes to ESBL-PE non-selectively, antimicrobial use favours strains resistant to drug taken and, simultaneously, any drug with resistance genetically linked to the drug used. Antibiotics taken during travel predispose to ESBL-PE with a high co-resistance rate. (C) 2017 The Author(s). Published by Elsevier Ltd.
  • Aro, Tuomas; Kantele, Anu (2018)
    Introduction: Antimicrobial resistance is increasing rapidly in countries with low hygiene levels and poorly controlled antimicrobial use. The spread of resistant bacteria poses a threat to healthcare worldwide. Refugees and migrants from high-prevalence countries may add to a rise in multidrug-resistant (MDR) bacteria in low-prevalence countries. However, respective data are scarce. Methods: We retrospectively collected microbiological and clinical data from asylum seekers and refugees treated at Helsinki University Hospital between January 2010 and August 2017. Results: Of 447 asylum seekers and refugees (Iraq: 46.5%; Afghanistan: 10.3%; Syria: 9.6%, Somalia: 6.9%); 45.0% were colonised by MDR bacteria: 32.9% had extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), 21.3% meticillin-resistant Staphylococcus aureus (MRSA), 0.7% carbap-enemase-producing Enterobacteriaceae (CPE), 0.4% multiresistant Pseudomonas aeruginosa (MRPA), 0.4% multiresistant Acinetobacter baumannii (MRAB); no vancomycin-resistant Enterococcus (VRE) were found. Two or more MDR bacteria strains were recorded for 12.5% of patients. Multivariable analysis revealed geographical region and prior surgery outside Nordic countries as risk factors of MRSA colonisation. Young age (<6 years old), short time from arrival to first sample, and prior hospitalisation outside Nordic countries were risk factors of ESBL-PE colonisation. Conclusion: We found MDR bacterial colonisation to be common among asylum seekers and refugees arriving from current conflict zones. In particular we found a high prevalence of MRSA. Refugees and migrants should, therefore, be included among risk populations requiring MDR screening and infection control measures at hospitals.
  • Kajova, Mikael; Khawaja, Tamim; Kangas, Jonas; Mäkinen, Hilda; Kantele, Anu (2021)
    Background: While 20–80% of regular visitors to (sub)tropical regions become colonised by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), those hospitalised abroad often also carry other multidrug-resistant (MDR) bacteria on return; the rates are presumed to be highest for interhospital transfers. Aim: This observational study assessed MDR bacterial colonisation among patients transferred directly from hospitals abroad to Helsinki University Hospital. We investigated predisposing factors, clinical infections and associated fatalities. Methods: Data were derived from screening and from diagnostic samples collected between 2010 and 2019. Risk factors of colonisation were identified by multivariable analysis. Microbiologically verified symptomatic infections and infection-related mortality were recorded during post-transfer hospitalisation. Results: Colonisation rates proved highest for transfers from Asia (69/96; 71.9%) and lowest for those within Europe (99/524; 18.9%). Of all 698 patients, 208 (29.8%) were colonised; among those, 163 (78.4%) carried ESBL-PE, 28 (13.5%) MDR Acinetobacter species, 25 (12.0%) meticillin-resistant Staphylococcus aureus, 25 (12.0%) vancomycin-resistant Enterococcus, 14 (6.7%) carbapenemase-producing Enterobacteriaceae, and 12 (5.8%) MDR Pseudomonas aeruginosa; 46 strains tested carbapenemase gene-positive. In multivariable analysis, geographical region, intensive care unit (ICU) treatment and antibiotic use abroad proved to be risk factors for colonisation. Clinical MDR infections, two of them fatal (1.0%), were recorded for 22 of 208 (10.6%) MDR carriers. Conclusions: Colonisation by MDR bacteria was common among patients transferred from foreign hospitals. Region of hospitalisation, ICU treatment and antibiotic use were identified as predisposing factors. Within 30 days after transfer, MDR colonisation manifested as clinical infection in more than 10% of the carriers.
  • Khawaja, T.; Kirveskari, J.; Johansson, S.; Väisänen, J.; Djupsjöbacka, A.; Nevalainen, A.; Kantele, A. (2017)
    Objectives: The pandemic spread of multidrug-resistant (MDR) bacteria poses a threat to healthcare worldwide, with highest prevalence in indigent regions of the (sub) tropics. As hospitalization constitutes a major risk factor for colonization, infection control management in low-prevalence countries urgently needs background data on patients hospitalized abroad. Methods: We collected data on 1122 patients who, after hospitalization abroad, were treated at the Helsinki University Hospital between 2010 and 2013. They were screened for methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), vancomycin-resistant enterococci, carbapenemase-producing Enterobacteriaceae (CPE), multiresistant Pseudomonas aeruginosa and multiresistant Acinetobacter baumannii. Risk factors for colonization were explored by multivariate analysis. Results: MDR colonization rates were higher for those hospitalized in the (sub) tropics (55%; 208/377) compared with temperate zones (17%; 125/745). For ESBL-PE the percentages were 50% (190/377) versus 12% (92/745), CPE 3.2% (12/377) versus 0.4% (3/745) and MRSA 6.6% (25/377) versus 2.4% (18/745). Colonization rates proved highest in those returning from South Asia (77.6%; 38/49), followed by those having visited Latin America (60%; 9/16), Africa (60%; 15/25) and East and Southeast Asia (52.5%; 94/179). Destination, interhospital transfer, short time interval to hospitalization, young age, surgical intervention, residence abroad, visiting friends and relatives, and antimicrobial use proved independent risk factors for colonization. Conclusions: Post-hospitalization colonization rates proved higher in the (sub) tropics than elsewhere; 11% (38/333) of carriers developed an MDR infection. We identified several independent risk factors for contracting MDR bacteria. The data provide a basis for infection control guidelines in low-prevalence countries (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.
  • Turunen, Katri A.; Kantele, Anu (2021)
    Background As antimicrobials increase the risk of acquiring multidrug-resistant (MDR) bacteria, unnecessary antibiotics should be avoided for travellers’ diarrhoea (TD). Antibiotics are recommended in TD accompanied by fever or incapacitation (TD justifying use of antibiotics, TDjuAB). Seeking tools for reducing antibiotic use, we explored factors predisposing to TDjuAB and scrutinized antibiotic treatment among those with TDjuAB [TDjuAB(+) subgroup] and those with diarrhoea not justifying antibiotics [TDjuAB(−) subgroup]. Methods We conducted a study among 370 prospectively recruited visitors to the tropics. Stool samples and questionnaires were collected before and after travel. Enteric pathogens were analysed by qPCR for enteropathogenic (EPEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC) and enteroinvasive (EIEC) E. coli/Shigella, Campylobacter, Salmonella, Yersinia and Vibrio cholerae, and for ETEC’s toxins LT (heat-labile), STh (human heat-stable) and STp (porcine heat-stable). TD was defined by the WHO criteria and TDjuAB as diarrhoea accompanied by fever, and/or disrupting or preventing daily activities. Multivariable analysis was applied—separately for travel-related factors and pathogens—to identify risk factors for TDjuAB(+). Results Among the 370 travellers, TD was contracted by 253 (68%), categorized as TDjuAB(+) in 93/253 (37%) and TDjuAB(−) in 160/253 (63%) of the cases. Antibiotics were used for TD by 41% in TDjuAB(+) and by 7% in the TDjuAB(−) group. Relative risk ratios (RRR)s are presented for both the TDjuAB(+) and the TDjuAB(−) groups. TDjuAB(+) was associated with long travel duration and young age. Among the 298 subjects not having taken antibiotics, increased RRRs were found e.g. for findings of Campylobacter coli/jejuni and ETEC’s STh toxin. Conclusions The first to analyse risk factors for TDjuAB, our study presents RRRs for demographic and behavioural factors and for various pathogens. Only less than half of those in the TDjuAB(+) group took antibiotics, which demonstrates that most cases meeting the current criteria recover without antimicrobial treatment.
  • Vilkman, Katri; Lääveri, Tinja; Pakkanen, Sari H.; Kantele, Anu (2019)
    Background: As antibiotics predispose travelers to acquiring multidrug-resistant intestinal bacteria, they should no longer be considered a mainstay for treating travelers' diarrhea. It has been claimed that stand-by antibiotics are justified as a means to avoid visits to local healthcare providers which often lead to polypharmacy. Method: We revisited the traveler data of 316 prospectively recruited volunteers with travelers' diarrhea by retrieving from questionnaires and health diaries information on antibiotic use, stand-by antibiotic carriage, and visits with local healthcare. Multivariable analysis was applied to identify factors associated with antibiotic use. Results: Among our 316 volunteers with travelers' diarrhea, however, carrying stand-by antibiotics seemed not to reduce the rate of healthcare-seeking; on the contrary, antibiotic use was more frequent among stand-by antibiotic carriers (34%) than non-carriers (11%). Antibiotics were equally taken for severe and incapacitating travelers' diarrhea, but compared to non-carriers, stand-by antibiotic carriers resorted to medication also for mild/moderate (38% vs. 4%) and non-incapacitating disease (29% vs. 5%). Antibiotic use was associated with stand-by antibiotic carriage (OR 7.2; 95%CI 2.8-18.8), vomiting (OR 3.5; 95%CI 1.3-9.5), incapacitating diarrhea (OR 3.6; 95%CI 1.3-9.8), age (OR 1.03; 95%CI 1.00-1.05), and healthcare visit for diarrhea (OR 465.3; 95%CI 22.5-9633.6). Conclusions: Carriage of stand-by antibiotics encouraged less cautious use of antibiotics. Recommendations involving prescription of antibiotics for all travelers require urgent revision.
  • Laaveri, Tinja; Sterne, Jesper; Rombo, Lars; Kantele, Anu (2016)
    Looking at the worldwide emergency of antimicrobial resistance, international travellers appear to have a central role in spreading the bacteria across the globe. Travellers' diarrhoea (TD) is the most common disease encountered by visitors to the (sub) tropics. Both TD and its treatment with antibiotics have proved significant independent risk factors of colonization by resistant intestinal bacteria while travelling. Travellers should therefore be given preventive advice regarding TD and cautioned about taking antibiotics: mild or moderate TD does not require antibiotics. Logical alternatives are medications with effects on gastrointestinal function, such as loperamide. The present review explores literature on loperamide in treating TD. Adhering to manufacturer's dosage recommendations, loperamide offers a safe and effective alternative for relieving mild and moderate symptoms. Moreover, loperamide taken singly does no predispose to contracting MDR bacteria. Most importantly, we found no proof that would show antibiotics to be significantly more effective than loperamide in treating mild/moderate TD. (C) 2016 The Authors. Published by Elsevier Ltd.